Nebulised liposomal amphotericin-B as maintenance therapy in allergic bronchopulmonary aspergillosis: a randomised, multicentre trial.

BACKGROUND: In allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission. METHODS: We performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal amphotericin-B or placebo for 6 months. The primary outcome was occurrence of a first severe clinical exacerbation within 24 months following randomisation. Secondary outcomes included the median time to first severe clinical exacerbation, number of severe clinical exacerbations per patient, ABPA-related biological parameters. RESULTS: Among 174 enrolled patients with ABPA from March 2015 through July 2017, 139 were controlled after 4-month attack treatment and were randomised. The primary outcome occurred in 33 (50.8%) out of 65 patients in the nebulised liposomal amphotericin-B group and 38 (51.3%) out of 74 in the placebo group (absolute difference -0.6%, 95% CI -16.8- +15.6%; OR 0.98, 95% CI 0.50-1.90; p=0.95). The median (interquartile range) time to first severe clinical exacerbation was longer in the liposomal amphotericin-B group: 337 days (168-476 days) versus 177 days (64-288 days). At the end of maintenance therapy, total immunoglobulin-E and Aspergillus precipitins were significantly decreased in the nebulised liposomal amphotericin-B group. CONCLUSIONS: In ABPA, maintenance therapy using nebulised liposomal amphotericin-B did not reduce the risk of severe clinical exacerbation. The presence of some positive secondary outcomes creates clinical equipoise for further research.

T helper 2 inflammatory markers are associated with recurrence in chronic rhinosinusitis with nasal polyps after endoscopic sinus surgery.

BACKGROUND: Despite maximum medical treatment and endoscopic sinus surgery (ESS), chronic rhinosinusitis with nasal polyps (CRSwNP) can require revision surgery. With a growing literature on the diversity of cytokine inflammation patterns in CRSwNP, an endotype-driven approach could lead to the identification of cytokine profiles that predict recurrence. METHODS: A monocentric longitudinal study was carried out until June 2019 following CRSwNP patients who underwent surgery for the first time between December 2010 and January 2012. The biomarker profiles were established on blood and nasal secretions at the time of the first surgery (Interleukin (IL)-5, IgE, IgA, eosinophilic cationic protein (ECP) and eosinophilic- derived neurotoxin (EDN)). Profiles were compared between the patients still controlled by medical treatment and the patients requiring revision surgery during the course of the follow-up period. RESULTS: Among the 48 patients initially enrolled in our study, 8 required revision surgery (16,7%). Clinical features (asthma, allergy, aspirin intolerance, active smoking) and levels of blood markers measured at the time of the first surgery were comparable between the 2 groups of patients. Levels of IL-5, IgE and ECP in nasal secretions were significantly increased in the group of patients needing revision surgery. CONCLUSIONS: Based on simple approach of nasal secretions sampling, we showed that a predominant T helper 2 proteins expression profile can be associated with recurrent CRSwNP after ESS. Initial immunoprofiling in CRSwNP disease may contribute to better predict the therapeutic response to optimal medical and surgical treatment, and help define the role of innovative targeted treatment, beside corticosteroids and ESS.

[Written action plans for asthma control: How are they used by pulmonologists in France?] / Les plans d'action écrits pour l'asthme : quel usage en font les pneumologues en France ?

INTRODUCTION: Despite evidence of the benefits of the written asthma action plans (WAP) in asthma control, they remain poorly applied. The aim of our study was to assess the practices of French-speaking pulmonologists and paediatricians in their use of WAP for asthma control and to analyse the contents of several WAPs routinely consulted in treatment of asthma patients. METHODS: Members of three French medical societies (SPLF, G2A, SP2A) were requested to share their WAPs for asthma patients and to participate in an online survey about the possible influence of these documents on their practices. RESULTS: Most (95%) of the 41 WAPs taken into consideration were symptom-based and 34% included peak expiratory flow measurement. All of these action plans were in full compliance with current guidelines. Among the 110 survey respondents, while 65% systematically provided a WAP to their asthma patients, only 30% often or always supplemented the written document with therapeutic education sessions. In almost every case, it was the doctor who presented the WAP to the patient, generally devoting to less than 10minutes to explanation of what they were handing out. CONCLUSIONS: In France, WAPs are generally presented to the patient by the physician, which probably limits the time devoted to explanation of their contents. Furthermore, WAPs are rarely reinforced with therapeutic education. The current study suggests ways of improving the utilization of WAPs in asthma care and treatment.

[Idiopathic pulmonary fibrosis: Desperately seeking a model]. / Fibrose pulmonaire idiopathique : recherche modèle désespérément.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal lung disease of which the origin and development mechanisms remain unknown. The few available pharmacological treatments can only slow the progression of the disease. The development of curative treatments is hampered by the absence of experimental models that can mimic the specific pathophysiological mechanisms of IPF. The aim of this mini-review is to provide an overview of the most commonly used experimental animal models in the study of IPF and to underline the urgent need to seek out new, more satisfactory models.

Role of CCL18 in asthma and lung immunity.

Allergic asthma is a prototypic Th2 mediated disease, where chemokines orchestrate the inflammatory cell recruitment. Most chemokines have a pro-inflammatory role. In this review, we focus on the potential role, in asthma and lung immunity, of CCL18 a chemokine both constitutively expressed at high levels in the lung and induced in inflammatory conditions. This chemokine is mainly produced by antigen presenting cells, and induced by Th2 type cytokines. The available data suggest that this chemokine may exhibit dual functions, with both pro- and anti-inflammatory properties, the latter through its ability to generate adaptive regulatory T cells in healthy subjects, with a loss of function in allergic patients. However, the functional implications are at the moment hampered by the lack of data on the nature of its putative receptor, and the absence of murine orthologue.

[Hyperventilation syndrome, definition, diagnostic and therapy]. / Le syndrome d'hyperventilation, définition, diagnostic et thérapeutique.

Hyperventilation syndrome (HVS) is a frequent disorder of which the etiology is unclear. Diagnosis is based on the ruling out of organic disease and, more positively, on results of the Nijmegen questionnaire, reproduction of symptoms during the hyperventilation provocation test (HPVT), and detected hypocapnia. Treatment is based on targeted respiratory physiotherapy consisting in voluntary hypoventilation and instructions to the patient on regular respiratory exercise over an appreciable period of time. Additional research is needed to evaluate the validity of current investigative tools leading to the diagnosis of hyperventilation syndrome and to appraise the efficacy of current respiratory physiotherapy methods.

[French practical guidelines for the diagnosis and management of IPF - 2021 update, full version]. / Recommandations pratiques pour le diagnostic et la prise en charge de la fibrose pulmonaire idiopathique ­ Actualisation 2021. Version intégrale.

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

[French practical guidelines for the diagnosis and management of IPF - 2021 update, short version]. / Recommandations pratiques pour le diagnostic et la prise en charge de la fibrose pulmonaire idiopathique ­ Actualisation 2021. Version courte.

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

[Management of asthma during pregnancy]. / Prise en charge de l'asthme chez la femme enceinte.

Asthma is the most common chronic condition in pregnant women. The risks of complications associated with asthma for the mother, the foetus and the pregnancy are mainly due to uncontrolled asthma and the occurrence of exacerbations. These events are promoted by the patient's difficulty in complying with treatment or by prescription insufficiency for an unjustified fear of teratogenicity. The challenge of the management of asthma during pregnancy is to ensure optimal maternal asthma control in order to prevent foetal hypoxia and thus, reduce the risk of complications. Preventing the occurrence of asthma symptoms and exacerbations, ensuring optimal lung function and managing the risk factors of poor asthma outcomes and comorbidities are the principles necessary to achieve this goal. Because of the low or non-existent risks of the main treatments of asthma for the foetus and the mother, it is widely recommended that all therapies initiated before conception are continued, in particular inhaled corticosteroids, and to adjust the dosage to the minimum effective dose. During the preconception period and throughout pregnancy, coordination of the different healthcare professionals (general practitioner, respiratory specialist and gynecologist) is essential, with the mother-to-be playing a central role in the management of her asthma.

[Physical activity and pulmonary rehabilitation in adults with asthma]. / Apports de l'activité physique et de la réadaptation respiratoire dans l'asthme de l'adulte.

Physical activity is reduced in people with asthma compared to the general population, especially in situations where patients have uncontrolled asthma symptoms, persistent airflow obstruction and other long-term medical problems, in particular obesity and anxiety. Exertional dyspnea, which is of multifactorial origin, is the main cause of reduced physical activity reduction and draws patients into a vicious circle further impairing quality of life and asthma control. Both the resumption of a regular physical activity, integrated into daily life, adapted to patients' needs and wishes as well as physical and environmental possibilities for mild to moderate asthmatics, and pulmonary rehabilitation (PR) for severe and/or uncontrolled asthmatics, improve control of asthma, dyspnea, exercise tolerance, quality of life, anxiety, depression and reduce exacerbations. A motivational interview to promote a regular programme of physical activity in mild to moderate asthma (steps 1 to 3) should be offered by all health professionals in the patient care pathway, within the more general framework of therapeutic education. The medical prescription of physical activities, listed in the Public Health Code for patients with long-term diseases, and pulmonary rehabilitation should be performed more often by specialists or the attending physician. Pulmonary rehabilitation addresses the needs of severe asthma patients (steps 4 and 5), and of any asthmatic patient with poorly controlled disease and/or requiring hospitalized for acute exacerbations, regardless of the level of airflow obstruction, and/or with associated comorbidities, and before prescribing biological therapies.

[A well-inked pneumonia can you decrypt it?] / Une pneumonie bien encrée à décrypter !

INTRODUCTION: We report a case of pneumonia associated with necrotic mediastinal lymph nodes in an immunocompetent patient. The case report illustrates the difficulties in making a diagnosis in necrotic mediastinal lymph nodes and discusses strategies to optimize sampling. OBSERVATION: A 21-year-old immunocompetent woman was admitted to hospital with dyspnea and fever occurring ten days after delivery. Physical examination, biological results and chest X-ray led to the diagnosis of right upper lobe pneumonia. Treatment with three broad-spectrum antibiotics was ineffective. Thoracic CT-scan showed compressive mediastinal and hilar necrotic adenopathies and consolidation of the right upper lobe. Bronchoscopy with bronchoalveolar lavage and transbronchial needle aspiration was non-diagnostic. A second bronchoscopy with bronchoalveolar lavage and transbronchial needle aspiration performed in close collaboration with the mycology laboratory led to the diagnosis of cryptococcosis. Antifungal therapy with fluconazole resulted in a complete resolution of clinical and radiological signs. CONCLUSION: Although it is extremely rare, pulmonary cryptococcosis should be considered in immunocompetent patients presenting with necrotic pneumonia. Effectiveness of lymph node sampling can be improved by collaboration between clinicians and microbiologists.

An avoidable cause of thymoglobulin anaphylaxis.

BACKGROUND: Thymoglobulin® (anti-thymocyte globulin [rabbit]) is a purified pasteurised, gamma immune globulin obtained by immunisation of rabbits with human thymocytes. Anaphylactic allergic reactions to a first injection of thymoglobulin are rare. CASE PRESENTATION: We report a case of serious anaphylactic reaction occurring after a first intraoperative injection of thymoglobulin during renal transplantation in a patient with undiagnosed respiratory allergy to rabbit allergens. CONCLUSIONS: This case report reinforces the importance of identifying rabbit allergy by a simple combination of clinical interview followed by confirmatory skin testing or blood tests of all patients prior to injection of thymoglobulin, which is formally contraindicated in patients with a history of hypersensitivity to rabbit proteins.

Diagnosis of primary antibody and complement deficiencies in young adults after a first invasive bacterial infection.

OBJECTIVES: Screening for primary immunodeficiencies (PIDs) in adults is recommended after two severe bacterial infections. We aimed to evaluate if screening should be performed after the first invasive infection in young adults. METHODS: Eligible patients were retrospectively identified using hospital discharge and bacteriology databases in three centres during a 3-year period. Eighteen to 40-year-old patients were included if they had experienced an invasive infection with encapsulated bacteria commonly encountered in PIDs (Streptococcus pneumoniae (SP), Neisseria meningitidis (NM), Neisseria gonorrhoeae (NG), Haemophilus influenzae (HI), or group A Streptococcus (GAS)). They were excluded in case of general or local predisposing factors. Immunological explorations and PIDs diagnoses were retrieved from medical records. Serum complement and IgG/A/M testings were systematically proposed at the time of study to patients with previously incomplete PID screening. RESULTS: The study population comprised 38 patients. Thirty-six had experienced a first invasive episode and a PID was diagnosed in seven (19%): two cases of common variable immunodeficiency revealed by SP bacteraemia, one case of idiopathic primary hypogammaglobulinaemia, and two cases of complement (C6 and C7) deficiency revealed by NM meningitis, one case of IgG2/IgG4 subclasses deficiency revealed by GAS bacteraemia, and one case of specific polysaccharide antibody deficiency revealed by HI meningitis. Two patients had previously experienced an invasive infection before the study period: in both cases, a complement deficiency was diagnosed after a second NM meningitis and a second NG bacteraemia, respectively. CONCLUSION: PID screening should be considered after a first unexplained invasive encapsulated-bacterial infection in young adults.

[Cardiopulmonary exercise testing in exercise-induced pulmonary hypertension]. / Intérêt de l'épreuve fonctionnelle d'exercice dans la détection de l'hypertension pulmonaire d'exercice.

OBJECTIVE: To determine the accuracy of cardiopulmonary exercise-testing (CPET) in detecting exercise-induced pulmonary hypertension. BACKGROUND: CPET plays a key role in the investigation of exertional breathlessness. Exercise-induced pulmonary hypertension has been recently demonstrated to be a cause of exertional dyspnea. However, the features of CPET associated with the condition are still unknown. METHODS: We prospectively studied CPET and exercise echo-cardiography characteristics in 39 patients complaining of exertional breathlessness. Patients could be divided into 3 groups as follows: 1) control subjects having normal pulmonary arterial pressure at rest [pulmonary arterial systolic pressure < 35 mmHg] and at peak exercise [pulmonary arterial systolic pressure < 45 mmHg]; 2) patients having exercise-induced PH; 3) patients having resting PH. Results from CPET have been analyzed within each group. RESULTS: Patients developing exercise-induced PH revealed an increased VD/VT ratio and CO2 gradient (P[a-ET]CO2) at peak exercise compared to controls (VD/VT at 0.38 +/- 0.1 vs 0.29 +/- 0.11 and P[a-ET]CO2 at 4,6 +/- 3,1 vs 1 +/- 3,8 mmHg). VD/VT and P[a-ET]CO2 were increased in patients with resting PH. A VD/VT ratio at peak exercise higher than 0.34 was 72.7% sensitive and 71% specific in predicting exercise-induced PH. Positive and negative predictive values were 72.7% and 70.1% respectively. CONCLUSION: Patients with exercise-induced PH did not decrease or may increase dead space during exercise. Therefore CPET may be a useful tool in selecting patients who need to undergo further exercise haemodynamic investigations.

[Pleural procedures in patients treated by platelet aggregation inhibitors: An opinion survey]. / Gestes pleuraux sous antiagrégants plaquettaires : une enquête d'opinion.

BACKGROUND: When pleural procedures (thoracocentesis, blind pleural biopsies and chest tube insertion) are required in patients taking long-term platelet aggregation inhibitors, the risk of bleeding must be balanced against the risk of arterial thrombosis. Currently, the bleeding risk of pleural procedures is poorly understood. OBJECTIVE: The objective of the survey was to gather the opinion of respiratory physicians regarding the bleeding risk of pleural procedures in patients taking platelet aggregation inhibitors. METHODS: We emailed a standardized questionnaire designed by the French National Authority for Health to 2697 French respiratory physicians. RESULTS: One hundred and eighty-eight of the 2697 questionnaires were returned (response rate: 7 %). The respiratory physicians declared that they performed an average of 8 pleural procedures per month. One hundred and seventy-five responders (95 %) practised pleural procedures in patients receiving platelet aggregation inhibitors; 68 of them (39 %) reported experiencing haemorrhagic complications. The bleeding risk associated with thoracentesis and chest tube insertion was considered minor by 97.8 and 65 % of responders respectively, whereas it was considered major for blind pleural biopsies by 73.4 %. Respiratory physicians were more reticent about performing pleural procedures in patients treated with clopidogrel than in those taking aspirin. CONCLUSION: This study provides an overview of how respiratory physicians perceive the bleeding risk associated with pleural procedures in patients taking platelet aggregation inhibitors.

[Importance of comorbidities in the anemia of COPD: Economic implications and 3-year survival analysis]. / Importance des comorbidités dans l'anémie de la BPCO : impact médico-économique et survie à 3 ans.

INTRODUCTION: Anemia occurs commonly in COPD and is associated with a poor prognosis. The role of comorbidities in this is suspected but poorly characterized and the economic implications of anemia combined with COPD in France have not been studied. The healthcare resource utilization and cost impact of anemia remain to be investigated. METHODS: One hundred and fifty-one COPD patients attending a pulmonology outpatient department during a 6 months period were retrospectively selected if they had undergone a pulmonary function test, a blood gas analysis or a blood count. The Charlson comorbidity index, resource utilization and economic data from the year before the diagnosis of anemia were compared between anemic and non-anemic patients as well as 3-year survival analysis. RESULTS: The prevalence of anemia was 18.5% and was not influenced by GOLD stage. The identification of anemia was similar from blood gas results and full blood count analysis. Comorbidities - mainly cardiovascular - were found in 86% of the anemic patients. The Charlson index was 5.4±2 in the anemic group compared to 4.1±1.5 in the non-anemic group (P<0.01). The Charlson index was the only predictive factor of anemia using logistic regression analysis. The 3-year mortality was 36% in the anemic versus 7% in the non-anemic group (P<0.05). The main factor identified which predicted 3-year mortality was the presence of anemia using logistic regression. Healthcare costs the year prior to the diagnosis of anemia were not significantly different between groups, but there was a tendency to an increase in the cost of the hospitalizations in the anemic group. CONCLUSIONS: Anemia is easy to diagnose in COPD from the blood gas analysis. It is frequently linked to the presence of comorbidities - mainly cardiovascular diseases - and is the more important predictive factor of the 3-year mortality. There was a tendency towards an increase in the costs of hospitalizations in anemic patients but this remains to be confirmed in a larger economic study.

Six-minute stepper test: a valid clinical exercise tolerance test for COPD patients.

INTRODUCTION: Exercise tolerance testing is an integral part of the pulmonary rehabilitation (PR) management of patients with chronic obstructive pulmonary disease (COPD). The 6-minute stepper test (6MST) is a new, well-tolerated, reproducible exercise test, which can be performed without any spatial constraints. OBJECTIVE: The aim of this study was to compare the results of the 6MST to those obtained during a 6-minute walk test (6MWT) and cardiopulmonary exercise testing (CPET) in a cohort of COPD patients. METHODS: Ninety-one COPD patients managed by outpatient PR and assessed by 6MST, 6MWT, and CPET were retrospectively included in this study. Correlations between the number of steps on the 6MST, the distance covered on the 6MWT, oxygen consumption, and power at the ventilatory threshold and at maximum effort during CPET were analyzed before starting PR, and the improvement on the 6MST and 6MWT was compared after PR. RESULTS: The number of steps on the 6MST was significantly correlated with the distance covered on the 6MWT (r=0.56; P<0.0001), the power at maximum effort (r=0.46; P<0.0001), and oxygen consumption at maximum effort (r=0.39; P<0.005). Performances on the 6MST and 6MWT were significantly improved after PR (570 vs 488 steps, P=0.001 and 448 vs 406 m, respectively; P<0.0001). Improvements of the 6MST and 6MWT after PR were significantly correlated (r=0.34; P=0.03). CONCLUSION: The results of this study show that the 6MST is a valid test to evaluate exercise tolerance in COPD patients. The use of this test in clinical practice appears to be particularly relevant for the assessment of patients managed by home PR.